The Human Genome Project: Mapping the Future

Sequencing the human genome has brought us unprecedented knowledge and controversy. Explore the issues involved in sequencing the human genome in this roundtable discussion with the researchers involved in the Human Genome Project.

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When The DNA Files first covered the Human Genome Project (HGP) in 1998, researchers had high hopes (and some concerns) about what would be done with the knowledge gained. In April 2003, 50 years to the month that James Watson and Francis Crick discovered DNA's structure, the National Human Genome Research Institute announced that the human genome sequence was complete. Today, the entire human genome sequence is available online (see http://www.ncbi.nih.gov/genome/guide/human/). The human genome sequence generated by the NIH does not represent any one person's genome. A large number of people donated samples, and only a few were sequenced. Thus researchers never knew the donors' identity. In 2007, though, the complete genome of a single individual, Dr. J. Craig Venter, was published. According to Venter's team of researchers, comparison of the two published genomes revealed that most variations result from single nucleotide differences. They proposed that the genetic variation between two individuals is as much as five times higher than previously estimated. While the genetic variation may be higher than expected, the number of genes in the human genome is surprisingly lower. While scientists originally estimated 80,000 to 140,000 genes, most now believe that the total number is closer to 25,000 or 30,000 (with some estimates even lower).

The success of the HGP has led to an explosion of sequencing projects. As of July 2007, the National Institutes of Health (NIH) listed 590 complete organism sequences, including those from bacteria, fungi, plants, and mammals. By knowing these sequences, researchers hope to discover the roles of viruses, pathogens, and genetic factors in human health and more accurately predict susceptibility and diagnose disease.

Knowledge of the human genome has enabled geneticists to assess susceptibility to many disorders, including fragile X syndrome, cystic fibrosis, Huntington's disease, Alzheimer's disease, and some inherited forms of cancer. GeneTests, an NIH-funded organization that promotes the appropriate use of genetic services in patient care and personal decision-making, reports that clinical genetic testing is currently available for about 1,133 diseases. Many of these tests are not predictive; rather, they can only determine if the individual has an increased risk for a genetic disease. Diagnostic tests, on the other hand, can identify hidden diseases with a high degree of accuracy. Neither screening nor diagnostic tests, however, can predict the severity of a disorder. For example, prenatal tests can diagnose cystic fibrosis, but they cannot tell a parent if their baby will have mild bronchial abnormalities or severe lung, pancreatic, and intestinal difficulties. Parents must decide what course of action they are comfortable with when the diagnosis is known but the prognosis is uncertain.

Most researchers agree that disease progression is influenced by a combination of genetic and environmental factors. In 2007, the NIH initiated the Human Microbiome Project, which aims to characterize the microbes that live in the human body and examine whether changes in the microbiome can be related to disease. In the human body, microbial cells are estimated to outnumber human cells by a factor of ten to one. Most of these microbial communities are not only harmless but also beneficial. For example, microbes help with digestion and nutrient absorption as well as protect from infection. In addition, researchers suspect that many diseases, including inflammatory bowel disease and Crohn's disease, are caused by a disruption in the normal microbial flora. However, not all microbes are beneficial. Viruses can cause severe sickness and even death. In 2003, scientists were able to sequence and identify the organism that causes severe acute respiratory syndrome (SARS) within two weeks of its detection in patients.

Gaining meaningful knowledge from DNA sequences will remain an important goal in biological research for a long time to come.

Original Program Description, 1998

The Human Genome Project is a result — at least indirectly — of the atomic bomb, and the project's implications for our global society may be similarly significant. The HGP grew out of the Department of Energy's research of genetic mutations caused by the development and use of nuclear weapons. In the mid 1980s a researcher at the DOE realized that it would be enormously useful to be able to compare the genome of a child with that of its parents — DNA base pair by DNA base pair — to uncover the mutations caused by radiation. Meetings were organized to discuss the technological hurdles and to introduce the idea to scientists from various disciplines.

There was some initial struggle. Many scientists worried that this study would suck money away from other research, and one complained, "Even if I had the sequence, I wouldn't know what to do with it." But the project gathered impetus in 1988 when the National Institutes of Health got involved. The biomedical implications of knowing the human genome were clear to most geneticists and biochemical researchers. By 1990 the U.S. Congress officially sanctioned the Human Genome Project, with research and oversight to be handled jointly by the DOE and NIH. Today most, if not all, scientists agree on the usefulness of this international 15-year effort to map and sequence all the genes in the human genome.

Sequencing the genome has brought us unprecedented knowledge. Researchers have identified genes that cause debilitating conditions. They have clues to some of the genetic mechanisms behind cancer and heart disease. The technologies that allow scientists to sequence genes also allow them to match DNA samples in criminal cases and paternity suits — and to know if a child will be born with Tay-Sachs or sickle-cell anemia. Anthropologists have a new tool for tracing the ancient migrations of people around the globe. And by comparing our DNA to the DNA of mice, worms, and plants, scientists have been able to quantify the interrelatedness of all life on the planet.

But there has been controversy. Some say that our technical knowledge has outpaced our ability to handle the social implications. We can test for ills that we can't treat. We'll test a fetus for Down syndrome, but we're unable to determine whether the child will be mildly or severely affected. We think there may be genes involved in personality traits, but we don't know the implications of telling a person that he or she is "predisposed" to, say, anxiety. Genetics show that the racial distinctions we make between people are cultural, not biological - so what does it mean to say that more African-Americans have sickle cell, or that more Euro-Americans have cystic fibrosis?

Explore these issues with the experts. Listen in on a roundtable discussion as NIH Human Genome Project director Francis Collins is joined by Georgia Dunston of the Howard University College of Medicine; Thomas Murray, then a member of the National Bioethics Advisory Commission; and Vicky Whittemore, from the National Tuberous Sclerosis Alliance.